Nikolaos Papadopoulos, MD, PhD: Dupilumab Safe and Effective in Pediatric Patients with Asthma

New data from the phase 3 of the LIBERTY VOYAGE ASTHMA study confirmed that the monoclonal antibody dupilumab caused significant reductions in the exacerbation rate and improvements in lung function and asthma control in pediatric patients with moderate-to-severe asthma

The findings were presented last week at the European Respiratory Society 2021 International Congress.

Leading investigator Nikolaos Papadopoulos, MD, PhD, Professor of Allergy & Pediatric Allergy at the University of Athens, Greece, elucidated on the phase 3 data in an email interview with HCPLive.

HCPLive: Could you provide brief overview of phase 3 of the LIBERTY ASTHMA VOYAGE study?

Papadopoulos: VOYAGE was a large, randomised trial looking into efficacy and safety of dupilumab, in children aged 6 to 11 years with uncontrolled moderate-to-severe asthma. Dupilumab is a monoclonal antibody targeting the common receptor of IL4 and IL13, two important molecules of inflammation.

HCPLive: Dupilumab was also used to treat pediatric patients with moderate-to-severe atopic dermatitis. Can you speak to the versatility of the biologic, and why you set out to treat moderate-to-severe asthma in pediatric patients as well?

Papadopoulos: Atopic dermatitis and asthma are both diseases of the immune system in which IL-4 and IL-13 play a key role. Thus, by blocking an important common pathway, dupilumab has the potential to improve both dermatitis and asthma and this has been confirmed in the clinical trials. It is reasonable that dupi may also be effective in other chronic conditions that are driven with the same type of inflammation – what we call ‘type-2 inflammation’.

HCPLive: Could you detail some of the complications that children with type 2 asthma face, and how dupilumab was effective in blocking the shared receptor component for IL-4 and IL-13, which are common drivers of type 2 inflammation?

Papadopoulos: Asthma is the most common chronic disease in children; a considerable proportion of them suffer from the uncontrolled moderate-to-severe form of the disease. Children who have asthma with underlying type 2 inflammation are more likely to have impaired lung function, frequent asthma attacks and poor quality of life. Previous results of the VOYAGE trial showed that dupilumab significantly reduced severe asthma exacerbations, and improved lung function and asthma control in children aged 6 to 11 years in uncontrolled, moderate-to-severe asthma with type 2 inflammation.

HCPLive: Can you detail some of the phenotypes that were included in this study, and the different responses to dupilumab?

Papadopoulos: This analysis looked at children with or without an allergic phenotype. An allergic phenotype was defined as total serum IgE ≥ 30 IU/mL and ≥ 1 perennial aeroallergen-specific IgE ≥ 0.35 kU/L at baseline. Regardless of allergic phenotype, dupilumab significantly reduced the rate of severe asthma attacks versus standard of care alone (placebo). In those with an allergic phenotype, dupilumab also significantly improved lung function and asthma control.

HCPLive: Dosing was based on the weight of the participants, and the average dose of Dupixent was 100 mg or 200 mg every 2 weeks. Were higher doses considered for this patient population?

Papadopoulos: The dosing regimen for children 6 to 11 years in this trial was selected based on the observed efficacy and safety in the dose-ranging study in adolescents and adults with moderate-to-severe asthma (Phase 2b study DRI12544), as well as the pharmacokinetic characterization and safety observation in the Phase 2 pediatric atopic dermatitis trial. This dosing regimen was designed to provide a clinical benefit and safety profile similar to that of older patients.

HCPLive: Dupilumab treatment resulted in a reduction of the annualized rate of severe asthma exacerbation events as well as significant improvements in percent predicted pre-bronchodilator FEV1 and ACQ-7-IA scores in patients with an allergic phenotype. Can you provide some details regarding the biologic’s efficacy in those areas?

Papadopoulos:

Severe Asthma Attacks (Exacerbations): Dupilumab significantly reduced the rate of severe asthma attacks with an average reduction of 62% over one year compared to placebo (p<0.001).

Lung Function (Percent Predicted Pre-bronchodilator FEV1): Already from the first dose there was an improvement in FEV1 that reached over 12% through the study, in comparison to 4%-5% in placebo.

Asthma Control (ACQ-7-IA): The LS mean difference vs matched placebo was -0.52 (95% CI -0.68 to -0.35) (p<0.001).

HCPLive: In participants with evidence of allergic asthma, dupilumab resulted in improvements in lung control, while no improvements were seen in the subgroup of patients with no evidence of allergic asthma regarding asthma control. Could you touch on that?

Papadopoulos:The lung function in children without evidence of allergic asthma also improved, but this was not statistically significant. It is possible that this is a result of the relatively small number of subjects in this group (25% of the total). Overall, the data are more robust in the allergic population.

HCPLive: Previous studies focused on the efficacy of dupilumab in patients 12 years and older, and this recent trial focused on pediatric patients ages 6 to 11. What is the next step in assessing the efficacy of the biologic, and what studies are you interested in conducting in the future?

Papadopoulos:Dupilumab has been studied across age groups in dermatologic, respiratory, and gastrointestinal conditions and the data so far have highlighted the far-reaching potential of addressing underlying type 2 inflammation with dupilumab in a variety of patient populations. It will be of great interest to explore the potential of dupilumab in influencing the natural course of asthma, possibly targeting younger children.